03/04/2008 - Press release
The study was published in the March online version of the prestigious journal “Lancet Oncology”.
The EPICURO project is coordinated in Spain by: Manolis Kogevinas and Núria Malats from the Centre for Research in Environmental Epidemiology (CREAL) and the Municipal Institute of Medical Research (IMIM-Hospital del Mar) in Barcelona; Francisco X. Real from the Municipal Institute of Medical Research (IMIM-Hospital del Mar); and Pompeu Fabra University in Barcelona. Specifically, on this occasion, the analysis was coordinated by the CREAL/IMIM-Hospital del Mar and the National Cancer Institute of the United States, with participation from the research group led by Dr. Manel Esteller of the Spanish National Cancer Research Centre in Madrid. Núria Malats and Francisco X. Real are currently heading their respective research groups at the Spanish National Cancer Research Centre in Madrid (CNIO).
In Spain, some 8,000 new cases of bladder cancer are diagnosed each year and 3,000 people die from the disease. With a five-year survival rate of 70%, it is a chronic disease that requires strict clinical monitoring and has a significant impact on quality of life. Bladder cancer is the tumour that incurs the highest health costs per patient.
At the experimental level, the importance of DNA methylation in determining chromatin structure had already been discovered. The addition of methyl groups (CH3) to the cytosine nucleotide, or DNA methylation, affects transcriptional ability (generally through the silencing of contiguous genes) and is related to genome stability. Genetic instability contributes to the development of cancer. The study has revealed that a reduction in overall DNA methylation levels (hypomethylation) is associated with a greater risk of developing bladder cancer.
According to Núria Malats “urinary bladder cancer has been an ideal model for these types of studies since the risk factors associated with the disease are already well-known”. Likewise, the majority of bladder cancers have a similar histological pattern and cells exfoliated from the urothelium or inside wall of the bladder can be easily obtained through urine.
Taking into account the existing risk factors as a whole, another important conclusion from this study has been, according to Manolis Kogevinas, “that the overall measure of DNA hypomethylation in the blood is, in and of itself, a risk factor independent of the other known risk factors for cancer, such as for example, tobacco consumption, despite the fact that the combined effect of the two factors greatly increases the risk of this neoplasia”.
To reach these conclusions, the research team has complied data from 1998 to 2001 on 775 bladder cancer patients from various regions of Spain (Catalonia, Asturias, Community of Valencia and the Canary Islands) within the EPICURO project. This information has been compared with data from a control group of 397 patients. The marker used in both groups has been the level of methylation in the cytosine nucleotide of the DNA of the white blood cells or leucocytes in the blood. Important information was also obtained from both groups regarding other risk factors associated with cancer development, such as eating habits and toxic habits (primarily alcohol and tobacco consumption).
The authors state that in addition to serving as a marker for bladder cancer risk, this information would most likely be just as valuable in the detection of other types of cancers as well.